Our recent NIH-supported studies have been successful in poviding some of the insights into the brainstem mechanisms involved in dental and facial pain and its control. Considerable gaps in our knowledge however still exist, particularly in terms of muscle pain mechanisms and processes involved in pain conditions that are associated with sensory loss (e.g., painful sensory neuropathies, causalgia, phantom limb and tooth pain). We will use our expertise with the trigeminal brain stem system to examine the responses of functionally identified single nociceptive and non-nociceptive neurons in the trigeminal spinal tract nucleus of the cat to muscle and thermal afferent stimulation, and to determine if this activity can be modulated by other orofacial sensory inputs and by descending influences from sites implicated in pain and analgesia. The underlying chemical mechanisms will also be studied in experiments of the effects on the modulating influences of antagonists to the possible chemicals involved, and in further experiments of the effects of the iontophoretic application of the putative neurotransmitters and neuromodulators. The effects of partial sensor loss on the functional organization of these neurons will also be investigated, by delineating the alterations in their response properties that may result from tooth pulp extirpation. The possible influence of subnucleus caudalis in functional alterations within subnucleus oralis will be determined, and the effects of pulp de-afferentation compared with the possible changes that sensory loss from other orofacial structures might induce.